Scientific article

Discriminating physiological from non‐physiological interfaces in structures of protein complexes: A community‐wide study

Published inProteomics, vol. 23, no. 17, 2200323
Publication date2023-06-27
First online date2023-06-27

Reliably scoring and ranking candidate models of protein complexes and assigning their oligomeric state from the structure of the crystal lattice represent outstanding challenges. A community‐wide effort was launched to tackle these challenges. The latest resources on protein complexes and interfaces were exploited to derive a benchmark dataset consisting of 1677 homodimer protein crystal structures, including a balanced mix of physiological and non‐physiological complexes. The non‐physiological complexes in the benchmark were selected to bury a similar or larger interface area than their physiological counterparts, making it more difficult for scoring functions to differentiate between them. Next, 252 functions for scoring protein‐protein interfaces previously developed by 13 groups were collected and evaluated for their ability to discriminate between physiological and non‐physiological complexes. A simple consensus score generated using the best performing score of each of the 13 groups, and a cross‐validated Random Forest (RF) classifier were created. Both approaches showed excellent performance, with an area under the Receiver Operating Characteristic (ROC) curve of 0.93 and 0.94, respectively, outperforming individual scores developed by different groups. Additionally, AlphaFold2 engines recalled the physiological dimers with significantly higher accuracy than the non‐physiological set, lending support to the reliability of our benchmark dataset annotations. Optimizing the combined power of interface scoring functions and evaluating it on challenging benchmark datasets appears to be a promising strategy.

  • Crystal contacts
  • Homodimers
  • Potential energy
  • Protein interactions
  • Protein structure
Affiliation Not a UNIGE publication
  • European Commission - ACCIÓ programme to foster mobility of researchers with a focus in applied research and technology transfer [801342]
  • European Commission - BioExcel Centre of Excellence for ComputationalBiomolecular Research [823830]
  • European Commission - Infinite Protein Self-Assembly in Health and Disease [819318]
  • Netherlands Organisation for Scientific Research (NWO) - Caught in the act: a combined magnetic resonance -modelling approach to capture cellular machines at work [718.015.001]
Citation (ISO format)
SCHWEKE, Hugo Charles Jean et al. Discriminating physiological from non‐physiological interfaces in structures of protein complexes: A community‐wide study. In: Proteomics, 2023, vol. 23, n° 17, p. 2200323. doi: 10.1002/pmic.202200323
Main files (1)
Article (Published version)
ISSN of the journal1615-9853

Technical informations

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